Background: In humans, erythromycin has been demonstrated to accelerate gallbladder emptying due to its motilin-like effects on the gastrointestinal tract. Recently, it was shown that clarithromycin, another macrolide, used for the eradication of Helicobacter pylori infection, also stimulated gastrointestinal motility in the fasting state. We conducted a comparative study on the effects of a single oral dose of clarithromycin and of erythromycin on gallbladder emptying in healthy subjects. Methods: Gallbladder emptying variables (residual volume, ejection fraction, area under emptying curve) were measured by ultrasound in 21 healthy subjects (11 males, 10 females, mean age 42.5+/-10.6 years). A test meal (14 g fat, 425 kcal) was ingested 30 min after a single oral dose (500 mg) of either clarithromycin or erythromycin, and the measurements were repeated the following day with the other drug (cross-over double-blind study). A control group consisting of 12 subjects (seven males, five females, mean age 50.7+/-8.2 years) was used to evaluate gallbladder emptying following the same test meal without drug administration. Differences between groups were analyzed using two-tailed Student's t-test for unpaired observations. Results: Gallbladder emptying at 60, 75, and 90 min was greater after erythromycin (P<0.05 at 90 min) and clarithromycin than it was in controls. The ejection fraction was significantly greater after clarithromycin (76.5%) and erythromycin (79.7%) than it was in controls. Gallbladder refilling occurred earlier after clarithromycin than after erythromycin. Conclusions: The prokinetic effect of clarithromycin on the gallbladder appears to be of similar amplitude but of shorter duration than that of erythromycin.